Aims: Despite dramatic increases in the number of young breast cancer survivors, relatively few studies have investigated factors that affect their health and quality of life. We are currently partnering with the YMCA to conduct a randomized controlled trial to test the ability of a combined resistance training and aerobic conditioning program to reduce two breast cancer treatment-related complications, the rapid loss of bone mineral density and weight gain brought about by an early and abrupt menopause. In this competitive supplement, we propose to greatly expand the depth of the current study by obtaining more precise measures of nutrient intake and body composition as well as measuring biomarkers that are both related to long-term health outcomes and are expected to be influenced by the exercise intervention. Adjuvant chemotherapy and the related weight gain can alter gonadal steroids (through direct effects on the ovary and indirectly through increased adipose tissue), cardiovascular risk factors, and calcitropic hormones. These alterations may adversely impact breast cancer survivors' future health and potentially increase their risk for breast cancer recurrence and mortality. Methods: Data collected at baseline and after the one year exercise intervention include: 1) additional measures of diet and body composition; 2) biomarkers assessing calcium metabolism, gonadal steroid status, and risk factors for the metabolic syndrome and cardiovascular disease. The primary analysis plan for the competitive supplement will focus on the changes from baseline to the end of the one-year intervention period in women randomized to the combined resistance and aerobic exercise intervention (N=160) compared to the control group (N=160) to determine effects of exercise on these biomarkers. In addition, the ability to control for dietary factors in statistical models of exercise effects and to analyze changes in body fat will be improved by the use of more precise measures of diet and body composition. Results: We will determine whether the exercise intervention is effective in improving biomarkers altered by chemotherapy weight gain that are related to increased risk of non-breast cancer morbidities as well as breast cancer recurrence and mortality. Implications: Findings from the parent grant and this competitive supplement may demonstrate the importance of favorable energy balance in not only reducing late effects of life-saving cancer treatment on the skeletal (parent grant), cardiovascular, and gonadal systems, but also improving the prognostic factors for breast cancer among women who were pre-menopausal at the time of their breast cancer diagnosis. [unreadable] [unreadable] [unreadable]